Five herpesviruses namely herpes simplex virus type 1 (HSV-1), type 2 (HSV-2) varicella-zoster virus (VZV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infect man and cause widespread infection. Primary infection usually results in the establishment of latent infection: Reactivation and reinfection occurs periodically. They also show in vitro transforming ability and some of them are associated with human cancers. These viruses encode a number of membrane associated proteins which are present on the virion envelopes and on the infected cell membranes. The long term objective of this research is to determine the antigenic relatedness between these membrane associated proteins. Our preliminary studies show antigenic cross reaction between these viruses and our immediate goals are now to identify and characterize the common membrane proteins and to investigate whether the response to common antigens can mediate in vitro and in vivo protection. Using our monoclonal antibodies we will affinity purify HSV and EBV glycoproteins and will raise monospecific antisera. We will also raise monoclonal antibodies to the cross reactive determinants by injecting mice with different combinations of cells infected with the five viruses. These antibodies will be tested for their cross reactivity with the five viruses in an ELISA test and in a surface immunofluorescence assay. The cross reacitve molecules will be further identified by immunoprecipitation of radiolabeled virus and infected cells. The cross reactive antibodies will be tested in various in vitro tests to determine their ability to modulate infection. These tests are: neutralization of virus infectivity, prevention of virus release, mediating lysis of infected cells through the interaction of complement and cells. The in vivo protective ability of the cross reactive monospecific antibodies and purified proteins will be tested by injecting them into mice and then challenging the HSV by footpad. These studies are significant since they will provide information on the functional role of the conserved proteins and will provide an important assessment of the feasibility of developing common immunogens for modification of disease induced by several of the members of the group.